Supramolecular 1D nanostructures have far reaching applications in chemistry, biology and materials science, owing in part to the ability to correlate properties and function with the nature of the individual building blocks. Among 1D nanostructures are cylindrical architectures generated from the stacking of homo-modular or hetero-modular rosettes formed through hydrogen bonding acceptor (A)-donor (D) interactions. Many examples of different sizes of rosettes including trimeric, tetrameric, pentameric, and hexameric have been showcased in the literature, a few of which have demonstrated further stacking into cylindrical architectures such as nanowires or nanofibers.
The molecular chemistry and supramolecular chemical biology of the pyrimido[4,5-d]pyrimidine shown in Fig. 1A and its analogues will be discussed here. This heterocycle, termed the GÙC motif herein, features a self-complementary triad of the ADD hydrogen bonding arrays of guanine (G) and DAA hydrogen bonding arrays of cytosine (C). In water, this motif undergoes an entropically driven, self-organization process to form hexameric rosettes maintained by 18 hydrogen bonds (Fig. 1B). Since the redundant NH group in the cytosine ring is functionalized, the molecule is less prone to pyrimidine-hydroxypyrimidine tautomerism, thereby effectively locking the DAA array for rosette formation, regardless of the solvent (aqueous or organic) it is dissolved in. Once these rosettes are generated, they then organize through p-stacking, van der Waals interactions and solvophobic effects to form discrete tubular architectures called rosette nanotubes (RNTs) that have an inner channel diameter of ca. 1.1 nm (Fig. 1C). These materials have shown unusual optical, chiroptical, and biological properties in solution as well as excellent thermal stability and mechanical resilience under shear force.
This talk will focus on the molecular and supramolecular design and characterization of various RNT classes; in particular recent applications in targeted drug and RNA delivery for pancreatic cancer therapy therapy will be discussed.
Dr. Fenniri received all his degrees from the Université de Strasbourg, France. After a postdoctoral fellowship at the Scripps Research Institute, CA, USA, he moved to Purdue University, IN, USA, where he initiated his independent academic career, and established the Purdue Laboratory for Chemical Nanotechnology (1999). In 2003, He joined the National Research Council as a founding member of the National Institute for Nanotechnology and as professor of chemistry and bioengineering at the University of Alberta (Canada, 2003-2013). Dr. Fenniri is currently Professor of Chemical Engineering and Bioengineering at Northeastern University, Boston, MA, USA. Dr. Fenniri’s contributions appeared in over 220 publications, 20 patents and patent applications, and over 500 contributed national and international conference papers. Dr. Fenniri has also lectured extensively around the globe and has been an invited professor at several institutes and universities.